The overall goal of this project is to define the mechanisms whereby electrolytes and water are secreted by the eccrine sweat glands. Human and monkey eccrine sweat glands will be isolated, cannulated, and stimulated in vitro and their secretory response to various pharmacological agents will be determined. The components of secreted sweat induced under different pharmacological agents and different incubation milieu will be analyzed in order to pinpoint the sites and mechanisms of electrolyte transport. The above parameters of normal sweat gland function will be compared with those of the sweat gland of cystic fibrosis in order to clarify the pathogenesis of this genetic endocrinopathy. Using similar cannulation methods, electrophysiological paramters such as potential difference and membrane resistance will be studied in order to correlate the electrical parameters with the secretory functions. The roles of Ca ions and cAMP in the stimulus-secretion coupling in the sweat gland will be further investigated. In particular, the amplifying effect of cholinergic stimulation on beta adrenergic stimulation in tissue cAMP accumulation will be studied, focusing on the role of Ca ions in such a synergistic interaction.